1. Field of the Invention
The present invention relates to modified release dosage forms containing sedative and hypnotic agents, preferably short acting sedatives and hypnotic agents. The dosage form of the present invention should provide therapeutically effective amounts of the sedative or hypnotic agent relatively quickly and maintain therapeutic levels for about four to eight hours after administration.
2. Description of the Related Art
In today's fast pace, instant information society, there is an increase in stress and sleep disorders. A number of sedatives and hypnotics have been developed to manage and control stress and sleep disorders. Some of the more common sedatives and hypnotic agents commercially available are VALIUM, XANAX, AMBIEN, SONATA and LUNESTA. These commercially available pharmaceutical products provide immediate release of the active pharmaceutical ingredient after administration allowing an immediate effect on the patient, however, they often do not maintain the effect long enough for a patient to obtain the recommended eight hours of sleep.
Although controlled release pharmaceutical dosage forms which release therapeutic amounts of the active ingredient over 8 to 24 hours are well known in the pharmaceutical industry, there are very few that control the release of sedative or hypnotic agents in a manner that allows a patient to obtain therapeutic amounts of a sedative or hypnotic agent rapidly after administration and maintain the therapeutic levels for about eight hours after administration so that a patient can obtain a full eight hours of restful sleep.
One controlled release product that attempts to obtain therapeutic amounts of a sedative or hypnotic agent rapidly after administration and maintain the therapeutic levels for about eight hours after administration so a patient can obtain a full eight hours of restful sleep is AMBIEN CR. AMBIEN CR is a biphasic tablet wherein one layer provides an immediate release amount of zolpidem tartrate and the other layer provides a slow or controlled release of zolpidem tartrate. See AMBIEN CR labeling. It is believed that the AMBIEN CR product is described in U.S. Pat. No. 6,514,531. According to the teachings of U.S. Pat. No. 6,514,531, the bilayer tablet should release at least 40% of the zolpidem tartrate within 30 minutes when tested in a type II dissolution apparatus according to the U.S. Pharmacopoeia in 0.01M HCl buffer at 37° C. Bilayer tablets such as AMBIEN CR can be difficult to manufacture because they require the precise measurement of the drug into two distinct regions of a tablet press and the compressing of these distinct regions into a unitary tablet. According to the product labeling for AMBIEN CR, a further drawback of the AMBIEN CR product is that bioavailability, as measured by area under the curve (AUC) and maximum plasma concentration (Cmax), was decreased by at least 20% and the median time to maximum plasma concentration (Tmax) was increased from 2 to 4 hours when the AMBIEN CR bilayered tablet was administered within 30 minutes after a meal. This decrease in bioavailability resulted in a slower or delayed onset of sleep.
United States Published Patent Application No. 2004/0258750 discloses another attempt to prepare a suitable controlled release dosage form for sedative and hypnotic agents. United States Published Patent Application No. 2004/0258750 discloses a multi-particulate dosage form that comprises a combination of immediate release pellets and delayed release pellets. The delayed release pellets are prepared by coating a drug core with a coating that is impermeable to the drug on contact with aqueous fluids but that breaks down or becomes permeable to the drug after a suitable period of time. As with the bilayered AMBIEN CR tablet, the multi-particulate dosage forms described in United States Published Patent Application No. 2004/0258750 can be difficult to manufacture.